Acetone → CID 72256353

HRID 1808770Notes

Reaction equation

HRID 1808770 reaction equation
[C:1]1(=[O:15])[N:6]2[CH2:7][CH2:8][C:9]3[CH2:10][C:11](=O)[CH:12]=[CH:13][C:4]([C:5]=32)=[CH:3][NH:2]1.[N:16]([O-])=[O:17].[Na+].CN(C)C=[O:23].Cl.CC(C)=O>C(O)(C)C.O>[NH:6]1[C:7]2=[CH:8][CH:9]=[CH:5][C:4]3=[C:3]2[N:2]([CH2:10][CH2:11][C:12](=[N:16][OH:17])[C:13]3=[O:23])[C:1]1=[O:15]

Participants

8

Reactant 5

HCID 180AcetoneHCID 313Hydrochloric Acid4×HCID 6228DimethylformamideHCID 23668193Sodium NitriteHCID 178515725HCID 178515725, compound3×

Product 1

HCID 72256353CID 72256353

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 3776IsopropanolSolvent2×

Conditions

Temperature
50 °C

Procedure

8,9-Dihydro-2H,7H-2,9a-diazabenzo[cd]azulene-1,6-dione (50 g; 92.4% purity; 0.228 mol) prepared in accordance with the procedure in Example 1 was dried and mixed with isopropanol (7.23 g; 0.12 mol; 0.53 eq) and water (3.01 g; 0.167 mol; 0.73 eq) (in alternative experiments and in production, 8,9-dihydro-2H,7H-2,9a-diazabenzo[cd]azulene-1,6-dione prepared in accordance with the procedure in Example 1 was instead used as centrifuge-wet material without the addition of water and isopropanol). The resulting wet 8,9-dihydro-2H-7H-2,9a-diazabenzo[cd]azulene-1,6-dione was combined with sodium nitrite (19.05 g at 99.3% purity; 0.274 mol; 1.2 eq) and N,N-dimethylformamide (800 g; 10.945 mol; 47.9 eq) in a stirred-tank reactor. The mixture was heated to 50° C., and then 32% HCl (41.65 g; 0.366 mol HCl; 1.6 eq HCl) was added over a 30 minute period. Toward the end of the HCl addition (i.e., after greater than 1 eq HCl had been added), the temperature quickly increased to 60-70° C. After all the HCl was added, the mixture was stirred at 60° C. for an additional 30 minutes. The mixture then was cooled to 35° C. over a 2- hour period. Next, water (224.71 g; 12.473 mol; 54.6 eq) was added over a 2-hour period. The resulting mixture was then cooled to 0° C. over a 2-hour period, and maintained at that temperature for 2 hours. Afterward, the solid 4,5-dihydro-imidazo[4,5,1-jk][1]benzazepin-2,6,7[1H]-trione-6-oxime product was removed by filtration and washed 4 times with water (70.1 ml each time; 15.566 mol total; 68.13 eq total) and once with acetone (115.9 g; 99.9% purity; 1.994 mol; 8.73 eq). All the above steps were conducted under a N2 atmosphere.

Workup

  1. customwas dried
  2. temperaturethe temperature quickly increased to 60-70° C
  3. temperatureThe mixture then was cooled to 35° C. over a 2- hour period
  4. temperatureThe resulting mixture was then cooled to 0° C. over a 2-hour period
  5. temperaturemaintained at that temperature for 2 hours
  6. customAfterward, the solid 4,5-dihydro-imidazo[4,5,1-jk][1]benzazepin-2,6,7[1H]-trione-6-oxime product was removed by filtration

Sources & evidence

ORD record
ord-c74d9179e60241248e4210d8aa01d9be
Source dataset
uspto-grants-2013_01
Patent number
US08362006B2

Reaction notes

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